Time-of-flight scatter rejection in x-ray radiography.

Objective.Time-of-flight (TOF) scatter rejection allows for identifying and discarding scattered photons without the use of an anti-scatter grid (ASG). Although TOF scatter rejection was initially presented for cone-beam computed tomography, we propose, herein, to extend this approach to x-ray radiography. This work aims to evaluate with simulations if TOF scatter rejection can outperform ASGs for radiography.Approach.GATE was used to simulate the radiography of a head and a torso and a water cylinder with bone inserts in a system with total timing jitters from 0 ps up to 500 ps full-width-at-half-maximum. The transmission factor of TOF scatter rejection for primary and scattered photons was evaluated as if it were a virtual ASG.Main results.With a total timing jitter of 50 ps, TOF scatter rejection can reach a selectivity of 4.93 with a primary photons transmission of 99%. Reducing the timing jitter close to 0 ps increases the selectivity up to 15.85 for a head and torso radiography, outperforming typical ASGs which usually have a selectivity from 2.5 to 10 with a primary photons transmission from 50% to 70%.Significance.This suggests that TOF scatter rejection may be suitable to replace ASGs in applications requiring lower radiation exposure if sufficiently low timing jitter is achieved.

Advances in stem cell and other therapies for Huntington's disease: An update.

Huntington's disease (HD) is a neurodegenerative disorder caused by an autosomal dominant mutation leading to an abnormal CAG repeat expansion. The result is the synthesis of a toxic misfolded protein, called the mutant huntingtin protein (mHTT). Most current treatments are palliative, but the latest research has expanded into multiple modalities, including stem cells, gene therapy, and even the use of 3D cell structures, called organoids. Stem cell research as a treatment for HD has included the use of various types of stem cells, such as mesenchymal stem cells, neural stem cells, embryonic stem cells, and even reprogrammed stem cells called induced pluripotent stem cells. The goal has been to develop stem cell transplant grafts that will replace the existing mutated neurons, as well as release existing trophic factors for neuronal support. Additionally, research in gene modification using CRISPR-Cas9, PRIME editing, and other forms of genetic modifications are continuing to evolve. Most recently, advancements in stem cell modeling have yielded 3D stem cell tissue models, called organoids. These organoids offer the unique opportunity to transplant a structured stem cell graft which, ideally, models normal human brain tissue more accurately. This manuscript summarizes the recent research in stem cells, genetic modifications, and organoids as a potential for treatment of HD.

Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

The association of Greig syndrome and mastocytosis reveals the involvement of the hedgehog pathway in advanced mastocytosis.

Mastocytosis is a heterogeneous disease characterized by an abnormal accumulation of mast cells (MCs) in 1 or several organs. Although a somatic KIT D816V mutation is detected in ∼85% of patients, attempts to demonstrate its oncogenic effect alone have repeatedly failed, suggesting that additional pathways are involved in MC transformation. From 3 children presenting with both Greig cephalopolysyndactyly syndrome (GCPS, Mendelian Inheritance in Man [175700]) and congenital mastocytosis, we demonstrated the involvement of the hedgehog (Hh) pathway in mastocytosis. GCPS is an extremely rare syndrome resulting from haploinsufficiency of GLI3, the major repressor of Hh family members. From these familial cases of mastocytosis, we demonstrate that the Hh pathway is barely active in normal primary MCs and is overactive in neoplastic MCs. GLI3 and KIT mutations had a synergistic, tumorigenic effect on the onset of mastocytosis in a GCPS mouse model. Finally, Hh inhibitors suppressed neoplastic MC proliferation in vitro and extend the survival time of mice with aggressive systemic mastocytosis (ASM). This work revealed, for the first time, the involvement of Hh signaling in the pathophysiology of mastocytosis and demonstrated the cooperative effects of the KIT and Hh oncogenic pathways in mice with ASM, leading to the identification of new promising therapeutic targets.

Effects of azacitidine in 93 patients with IDH1/2 mutated acute myeloid leukemia/myelodysplastic syndromes: a French retrospective multicenter study.

Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) mutations in Myeloid Neoplams (MNs) exhibit DNA hypermethylation via 2-hydroxyglutarate (2HG) over-production. Clinical impact of azacitidine (AZA) remains inconsistent in IDH1/2-mutated MNs and the potential of serum 2HG as a suitable marker of response to AZA is unknown. To address these questions, we retrospectively analyzed 93 MNs patients (78 AML, 11 MDS, 4 CMML) with IDH1/2 mutations treated with AZA. After a median of 5 cycles of AZA, overall response rate was 28% (including 15% complete remission) and median OS was 12.3 months (significantly shorter in AML compared to MDS/CMML patients). In multivariate analysis of AML patients, DNMT3A mutation was associated with shorter OS while IDH1/2 mutation subtypes had no independent impact. No difference was observed in serum 2HG levels upon AZA treatment between responding and refractory patients suggesting that serum 2HG cannot be used as a surrogate marker of AZA response.

Time-of-flight computed tomography - proof of principle.

Computed tomography has greatly improved over the last decade, especially through x-ray dose exposure reduction while maintaining image quality. Herein, a new concept is proposed to improve the contrast-to-noise ratio (CNR) by including the time-of-flight (TOF) information of individual photons to obtain further insight on the photon's trajectory and to reject scatter contribution. The proof of the concept relies on both simulation and experimental measurements in a cone-beam computed tomography arrangement. Results show a statistical difference between the TOF of scattered and primary photons exploitable in TOF computed tomography. For a large volume of the size of a human abdomen, a scatter reduction from 296% to 4% is achieved in our simulation setup with perfect timing measurements which yields a 110% better CNR, or a dose reduction by a factor of four. Cup artifacts are also reduced from 24.7% to 0.8%, and attenuation inaccuracies are improved from -26.3% to -0.8%. With 100 ps and 10 ps FWHM timing jitters, respectively 75% and 95% of the scatter contribution can be removed with marginal gains below 10 ps. Experimental measurements confirm the feasibility of measuring statistical differences between the TOF of scattered and primary photons.

Transplantation of mesenchymal stem cells genetically engineered to overexpress interleukin-10 promotes alternative inflammatory response in rat model of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause for long-term disability, yet the treatments available that improve outcomes after TBI limited. Neuroinflammatory responses are key contributors to determining patient outcomes after TBI. Transplantation of mesenchymal stem cells (MSCs), which release trophic and pro-repair cytokines, represents an effective strategy to reduce inflammation after TBI. One such pro-repair cytokine is interleukin-10 (IL-10), which reduces pro-inflammatory markers and trigger alternative inflammatory markers, such as CD163. In this study, we tested the therapeutic effects of MSCs that were engineered to overexpress IL-10 when transplanted into rats following TBI in the medial frontal cortex. METHODS: Thirty-six hours following TBI, rats were transplanted with MSCs and then assessed for 3 weeks on a battery of behavioral tests that measured motor and cognitive abilities. Histological evaluation was then done to measure the activation of the inflammatory response. Additionally, immunomodulatory effects were evaluated by immunohistochemistry and Western blot analyses. RESULTS: A significant improvement in fine motor function was observed in rats that received transplants of MSCs engineered to overexpress IL-10 (MSCs + IL-10) or MSCs alone compared to TBI + vehicle-treated rats. Although tissue spared was unchanged, anti-inflammatory effects were revealed by a reduction in the number of glial fibrillary acidic protein cells and CD86 cells in both TBI + MSCs + IL-10 and TBI + MSC groups compared to TBI + vehicle rats. Microglial activation was significantly increased in the TBI + MSC group when compared to the sham + vehicle group. Western blot data suggested a reduction in tumor necrosis factor-alpha in the TBI + MSCs + IL-10 group compared to TBI + MSC group. Immunomodulatory effects were demonstrated by a shift from classical inflammation expression (CD86) to an alternative inflammation state (CD163) in both treatments with MSCs and MSCs + IL-10. Furthermore, co-labeling of both CD86 and CD163 was detected in the same cells, suggesting a temporal change in macrophage expression. CONCLUSIONS: Overall, our findings suggest that transplantation of MSCs that were engineered to overexpress IL-10 can improve functional outcomes by providing a beneficial perilesion environment. This improvement may be explained by the shifting of macrophage expression to a more pro-repair state, thereby providing a possible new therapy for treating TBI.

Radioimmunotherapy ((90) Y-Ibritumomab Tiuxetan) for Posttransplant Lymphoproliferative Disorders After Prior Exposure to Rituximab.

Posttransplantation lymphoproliferative disorders (PTLDs) are life-threatening complications after solid organ and hematopoietic stem cell transplantation. Only half of CD20-positive PTLDs respond to rituximab monotherapy, and outcomes remain poor for patients with relapsed/refractory disease, especially those who do not qualify for an anthracycline containing regimen due to frailty or comorbidities. Radioimmunotherapy (RIT) might be an option in this particular setting. We report a panel of eight patients with rituximab refractory/relapsed CD20-positive PTLDs including three ineligible for subsequent CHOP-like chemotherapy who received (90) Y-Ibritumomab tiuxetan as a single agent (n = 7) or combined to chemotherapy (n = 1). Five out of eight patients were kidney transplant recipients, while 2/8 had a liver transplant and 1/8 had a heart transplant. Patients received a median of two previous therapies. Overall response rate was 62.5%. Importantly, all responders achieved complete response. At a median follow-up of 37 months [5; 84], complete response was ongoing in four patients. Toxicity was predominantly hematological and easily manageable. No graft rejection was noticed concomitantly or following RIT administration despite immunosuppression reduction after diagnosis of PTLDs. This report emphasizes the potential efficiency of salvage RIT for early rituximab refractory PTLDs without any unexpected toxicity.

Bone-marrow-derived mesenchymal stem cells attenuate cognitive deficits in an endothelin-1 rat model of stroke.

PURPOSE: Stroke is the third leading cause of death and permanent disability in the United States, often producing long-term cognitive impairments, which are not easily recapitulated in animal models. The goals of this study were to assess whether: (1) the endothelin-1 (ET-1) model of chronic stroke produced discernable cognitive deficits; (2) a spatial operant reversal task (SORT) would accurately measure memory deficits in this model; and (3) bone-marrow-derived mesenchymal stem cells (BMMSCs) could reduce any observed deficits. METHODS: Rats were given unilateral intracerebral injections of vehicle or ET-1, a stroke-inducing agent, near the middle cerebral artery. Seven days later, they were given intrastriatal injections of BMMSCs or vehicle, near the ischemic penumbra. The cognitive abilities of the rats were assessed on a novel SORT, which was designed to efficiently distinguish cognitive deficits from potential motoric confounds. RESULTS: Rats given ET-1 had significantly more cognitive errors at six weeks post-stroke on the SORT, and that these deficits were attenuated by BMMSC transplants. CONCLUSIONS: These findings indicate that: (1) the ET-1 model produces chronic cognitive deficits; (2) the SORT efficiently measures cognitive deficits that are not confounded by motoric impairment; and (3) BMMSCs may be a viable treatment for stroke-induced cognitive dysfunction.

Assessing the potential clinical utility of transplantations of neural and mesenchymal stem cells for treating neurodegenerative diseases.

Treatments for neurodegenerative diseases have little impact on the long-term patient health. However, cellular transplants of neuroblasts derived from the aborted embryonic brain tissue in animal models of neurodegenerative disorders and in patients have demonstrated survival and functionality in the brain. However, ethical and functional problems due to the use of this fetal tissue stopped most of the clinical trials. Therefore, new cell sources were needed, and scientists focused on neural (NSCs) and mesenchymal stem cells (MSCs). When transplanted in the brain of animals with Parkinson's or Huntington's disease, NSCs and MSCs were able to induce partial functional recovery by promoting neuroprotection and immunomodulation. MSCs are more readily accessible than NSCs due to sources such as the bone marrow. However, MSCs are not capable of differentiating into neurons in vivo where NSCs are. Thus, transplantation of NSCs and MSCs is interesting for brain regenerative medicine. In this chapter, we detail the methods for NSCs and MSCs isolation as well as the transplantation procedures used to treat rodent models of neurodegenerative damage.

Rituximab-cyclophosphamide-dexamethasone combination in the management of autoimmune cytopenias associated with chronic lymphocytic leukemia.

We report our experience on rituximab-cyclophosphamide-dexamethasone (RCD) combination therapy for the treatment of autoimmune disorders (AIDs) in 48 chronic lymphocytic leukemia (CLL) patients. Overall, 81% of patients were relapsing for AID after previous treatment with corticosteroids, splenectomy, rituximab or alemtuzumab. Diagnosis of AID was autoimmune hemolytic anemia (AIHA) in 26 (54%), autoimmune thrombocytopenia (AITP) in 9 (18.8%), Evan's syndrome in 8 (16.7%) and pure red cell aplasia (PRCA) in 5 patients (10.5%). Median time of autoimmune disorder (AID) onset from CLL diagnosis was 60 months (range: 0-240), and CLL was considered progressive in 40% of subjects upon AID diagnosis (complex AID). Median hemoglobin pre-treatment was 7.7 g/100 ml, and median platelet count 36.5 × 10(9)/l, returning to a median of 12.5 /100ml and 37.5 × 10(9)/l, respectively. Overall, an 89.5% response rate was obtained with this combination, irrespective of the AID type. Relapse occurred in 19 patients (39.6%). Median duration of response for autoimmunity (DR-AI) was 24 months, but DR-AI was higher for patients presenting: (1) AID early during CLL course (<3 years), or (2) both PRCA and AIHA. Median time to CLL progression in 48 patients was 16 months, but this time was statistically shorter for Evan's syndrome and AITP patients as compared with AIHA and PRCA patients. This study emphasizes the relevance of CLL-directed immune chemotherapy in the management of CLL-associated AID.

[Waldenström's macroglobulinemia]. / Macroglobulinémie de Waldenström.

Waldenström's macroglobulinemia (WM) is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells, along with the presence of an IgM monoclonal gammopathy in the blood. WM remains incurable with a median of 8-year of overall survival for patients with symptomatic WM. Treatment is postponed for asymptomatic patients and progressive anemia is the most common indication for initiation of treatment. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab, either alone or in combination. Studies involving new combination chemotherapy are ongoing and preliminary results are encouraging. However, there are several limitations to these approaches. The complete response rate is low and the treatment free survival is short in many patients, no specific agent or regimen has been shown to be superior to another, and no treatment has been specifically approved for WM. As such, new therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to better target therapeutics for this malignancy. These efforts have led to the development of proteasome inhibitors as bortezomib, several Akt/mTor inhibitors, such as perifosine and Rad001. Many other agents and monoclonal antibodies are currently being tested in clinical trials and seem promising. This article provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM.

New lines of GFP transgenic rats relevant for regenerative medicine and gene therapy.

Adoptive cell transfer studies in regenerative research and identification of genetically modified cells after gene therapy in vivo require unequivocally identifying and tracking the donor cells in the host tissues, ideally over several days or for up to several months. The use of reporter genes allows identifying the transferred cells but unfortunately most are immunogenic to wild-type hosts and thus trigger rejection in few days. The availability of transgenic animals from the same strain that would express either high levels of the transgene to identify the cells or low levels but that would be tolerant to the transgene would allow performing long-term analysis of labelled cells. Herein, using lentiviral vectors we develop two new lines of GFP-expressing transgenic rats displaying different levels and patterns of GFP-expression. The "high-expresser" line (GFP(high)) displayed high expression in most tissues, including adult neurons and neural precursors, mesenchymal stem cells and in all leukocytes subtypes analysed, including myeloid and plasmacytoid dendritic cells, cells that have not or only poorly characterized in previous GFP-transgenic rats. These GFP(high)-transgenic rats could be useful for transplantation and immunological studies using GFP-positive cells/tissue. The "low-expresser" line expressed very low levels of GFP only in the liver and in less than 5% of lymphoid cells. We demonstrate these animals did not develop detectable humoral and cellular immune responses against both transferred GFP-positive splenocytes and lentivirus-mediated GFP gene transfer. Thus, these GFP-transgenic rats represent useful tools for regenerative medicine and gene therapy.

In vitro efficacy of nitro- and halogeno-thiazolide/thiadiazolide derivatives against Sarcocystis neurona.

Sarcocystis neurona is an obligate intracellular parasite that causes equine protozoal myeloencephalitis (EPM). The aim of this work was to document inhibitory activities of nitazoxanide (NTZ, [2-acetolyloxy-N-(5-nitro 2-thiazolyl) benzamide]) and new thiazolides/thiadiazolides on S. neurona in vitro development, and investigate their structure-activity relationships. S. neurona was grown in bovine turbinate cell cultures. At concentrations varying from 1.0 to 5.0mg/L, nitazoxanide and 21 of 32 second generation thiazolide/thiadiazolide agents exerted a > or =95% maximum inhibition on S. neurona development. Most active agents were either NO(2) or halogen substituted in position 5 of their thiazole moiety. In contrast, other 5-substitutions such as hydrogen, methyl, SO(2)CH(3), and CH(3) negatively impacted activity. Compared with derivatives with an acetylated benzene moiety, deacetylated compounds which most probably represent primary metabolites exhibited similar inhibitory activities. Present data provide the first evidence of in vitro inhibitory activities of nitazoxanide and new thiazolides/thiadiazolides on S. neurona development. Active halogeno-thiazolide/thiadiazolides may provide a valuable nitro-free alternative to nitazoxanide for EPM treatment depending on further evaluation of their in vivo activities.

Clinical trial: randomized, double-blind, placebo-controlled study of nitazoxanide monotherapy for the treatment of patients with chronic hepatitis C genotype 4.

BACKGROUND: Nitazoxanide, licensed in the US for treatment of Cryptosporidium parvum and Giardia lamblia, inhibits hepatitis C virus replication in replicon systems. AIM: To evaluate the safety and efficacy of nitazoxanide monotherapy for the treatment of chronic hepatitis C. METHODS: This multicentre, randomized, double-blind, placebo-controlled study randomized 50 adult patients with chronic hepatitis C genotype 4 at three centres in Egypt to nitazoxanide 500 mg tablet or placebo twice daily for 24 weeks. Patients were followed up every 4 weeks during treatment and for 24 weeks after therapy. RESULTS: Seven of 23 patients (30.4%) in the nitazoxanide group achieved undetectable serum HCV RNA compared to 0 of 24 in the placebo group during therapy (P = 0.004). Each of the seven responders had baseline HCV RNA levels < or =400 000 IU/mL. Six of the seven virological responders were followed up for 24 weeks after the end of treatment, and four patients (17.4% of 23 treated) had a sustained virological response. Adverse events were similar in the nitazoxanide and placebo groups. CONCLUSION: Nitazoxanide monotherapy is safe and effective in achieving sustained virological response in a modest number of patients with chronic hepatitis C genotype 4, particularly in patients with low baseline serum HCV RNA levels.

Nitazoxanide in the treatment of viral gastroenteritis: a randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Enteric viruses including noroviruses and rotavirus are leading causes of diarrhoeal disease and gastroenteritis worldwide, and there is no effective treatment. AIM: To evaluate nitazoxanide, a thiazolide anti-infective agent, in treating viral gastroenteritis in adults and adolescents. METHODS: 50 out-patients at least 12 years of age (mean 33.5 years) presenting with diarrhoea and stool-positive by enzyme-linked immunosorbent assay for norovirus, rotavirus or adenovirus were enrolled in a double-blind, placebo-controlled clinical trial. Patients were randomly assigned either nitazoxanide 500 mg or placebo twice daily for 3 days. The primary end point was time from first dose to resolution of symptoms. Analysis was modified intent-to-treat for 45 patients, excluding five patients with other identified enteropathogens at baseline. RESULTS: The median time from first dose to resolution of symptoms was 1.5 days (IQR: 0.5-2.5) for nitazoxanide-treated patients and 2.5 days (IQR: 1.5-4.5) for the placebo group. Significant reductions in time to resolution of symptoms were observed for all patients analysed (P < 0.0001) and for subsets of patients with rotavirus (P = 0.0052) and norovirus (P = 0.0295). The number of patients with adenovirus (n = 5) was too small to draw any conclusion. No significant adverse events were reported. CONCLUSIONS: Nitazoxanide may play an important role in managing viral gastroenteritis in adults.

Nitazoxanide in the treatment of acquired immune deficiency syndrome-related cryptosporidiosis: results of the United States compassionate use program in 365 patients.

BACKGROUND: Cryptosporidiosis in patients with acquired immune deficiency syndrome is a serious, life-threatening disease. AIM: A large compassionate use clinical trial was conducted in the USA to make nitazoxanide available to patients with acquired immune deficiency syndrome-related cryptosporidiosis and to collect data related to safety and effectiveness of the drug in this population. METHODS: Patients at least 3 years of age with acquired immune deficiency syndrome, diarrhoea (> or =4 stools/day for >2 weeks) and Cryptosporidium-positive stools received 500-1500 mg of nitazoxanide twice daily. Patients were evaluated at weeks 1, 2, 4 and monthly thereafter for drug safety and effectiveness including the stool examinations, review of symptoms and patient diaries. Data analysis for clinical and parasitological response was intention-to-treat. RESULTS: Three hundred and sixty-five patients were enrolled at 165 study centres throughout the USA. The duration of treatment ranged from 1 to 1,528 days (median 62 days). Among the 357 patients included in the intent-to-treat analysis, 209 (59%) achieved a sustained clinical response while on treatment. Clinical responses were closely associated with Cryptosporidium-negative stools (P < 0.0001). No safety issues were identified at doses up to 3000 mg/day or for long durations of treatment. CONCLUSIONS: Nitazoxanide can be considered useful therapy for treatment of with acquired immune deficiency syndrome-related cryptosporidiosis.

Efficacy of nitazoxanide and paromomycin in biliary tract cryptosporidiosis in an immunosuppressed gerbil model.

OBJECTIVES: To evaluate the efficacy of nitazoxanide and paromomycin in biliary tract cryptosporidiosis in an immunosuppressed Mongolian gerbil (Meriones unguiculatus) model. METHODS: Gerbils (1-month-old) were dexamethasone-immunosuppressed for 10 days and challenged orally with 10(5) Cryptosporidium parvum oocysts. From day 0 to day 12 post-infection, one group (n=14) was treated with 200 mg/kg/day nitazoxanide and another (n=15) with 100 mg/kg/day paromomycin. Infection and efficacy of nitazoxanide and paromomycin were assessed by measuring oocyst shedding in faeces, biliary tract and ileum histological examination. RESULTS: In nitazoxanide-treated and paromomycin-treated groups as compared with untreated animals (P<0.05), oocyst shedding was partially suppressed in a similar manner (P>0.05). Parasites were present in histological sections of the ileal mucosa of 16/16 infected untreated animals versus 3/14 and 6/15 in the nitazoxanide-treated and the paromomycin-treated groups, respectively (P<0.05). In addition, gall bladder infection was less frequent in nitazoxanide-treated (2/14, P<0.01) and paromomycin-treated (5/15, P=0.07) animals than in untreated controls (9/16). No histological alteration of biliary mucosa was observed in both treated and untreated infected gerbils. CONCLUSIONS: Present data support the efficacy of nitazoxanide and, to a lesser extent, paromomycin on biliary C. parvum infection in gerbils, and prompt further investigation of the potential clinical benefits of nitazoxanide in treating human biliary cryptosporidiosis.